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Environmental Science and Pollution... Dec 2021The present study has been carried out to evaluate the effects of piperazine and EDTA (ethylenediaminetetraacetic acid) in the garden snail, Cornu aspersum. EDTA and...
The present study has been carried out to evaluate the effects of piperazine and EDTA (ethylenediaminetetraacetic acid) in the garden snail, Cornu aspersum. EDTA and piperazine-like chemicals are widely used in various pharmaceutical, household, and industrial applications. The snails after collection were kept in different earthen pots and treated with these chemicals at different concentrations. A higher concentration of these chemicals led to a change in foot color from light to dark brown and loss in average weight with time. It has been found that a 10-fold increase in piperazine and EDTA concentration reduces weight by approximately 12.7- and 11.6-fold, respectively. Further, the study provides an insight into the altered antimicrobial activity of crude extract when treated with ligands. Additionally, the variations in the electrolytes in the mucus sample have been observed with the mean standard deviation (± SD) of 6.4 and 2.4 for Na and K ions, respectively.
Topics: Animals; Anti-Infective Agents; Edetic Acid; Electrolytes; Piperazine; Snails
PubMed: 34327636
DOI: 10.1007/s11356-021-15543-5 -
Environmental Entomology Jun 2023Recently, there are many studies suggesting antibacterial, antifungal, and anthelmintic agents as alternative chemicals to insecticides. In this study, the oxidative and...
Recently, there are many studies suggesting antibacterial, antifungal, and anthelmintic agents as alternative chemicals to insecticides. In this study, the oxidative and genotoxic effect of Piperazine, a clinically important hexahydropyrazine anthelmintic, on Galleria mellonella L. hemolymph tissue by adding artificial diet were investigated. Galleria mellonella larvae were reared until 7th larval stage in artificial diet containing 0.001, 0.01, 0.1, and 1 g piperazine per 100 g of diet. Using hemolymph collected from 7th-instar larvae, the amount of lipid peroxidation final product malondialdehyde (MDA), protein oxidation product protein carbonyl (PCO), and detoxification enzymes glutathione S-transferase (GST) and cytochrome P450 monooxygenase (cyt P450) activity, comet assay were measured. According to the results obtained, when the piperazine high concentrations tested with the control group were compared, statistically significant differences were found in MDA, PCO content, cyt P450, GST activity, and comet assay in the hemolymph of the insect. While MDA content was 0.01 ± 0.0021 nmol/mg protein in the control group, this amount increased approximately 2-fold at the highest concentration (0.0231 ± 0.0050 nmol/mg protein). On the other hand, when the control group and the highest piperazine concentration were compared in the GST and cyt P450 activity, it was determined that there was a statistically significant increase. We obtained similar results in comet assay and micronucleus formation data. This study showed that the tested piperazine concentrations caused significant changes in the detoxification capacity, oxidative stress, and genotoxic markers in the insect's hemolymph tissue.
Topics: Animals; Hemolymph; Piperazine; Moths; Larva; Oxidative Stress; DNA Damage
PubMed: 37043612
DOI: 10.1093/ee/nvad028 -
Critical Reviews in Food Science and... Mar 20172,5-Diketopiperazines (2,5-DKPs) have been found to occur in a wide range of food and beverages, and display an array of chemesthetic effects (bitter, astringent,... (Review)
Review
2,5-Diketopiperazines (2,5-DKPs) have been found to occur in a wide range of food and beverages, and display an array of chemesthetic effects (bitter, astringent, metallic, and umami) that can contribute to the taste of a variety of foods. These smallest cyclic peptides also occur as natural products and have been found to display a variety of bioactivities from antibacterial, antifungal, to anthroprotective effects and have the potential to be used in the development of new functional foods. An overview of the synthesis of these small chiral molecules and their molecular properties is presented. The occurrence, taste, and bioactivity of all simple naturally occurring 2,5-DKPs to date have been reviewed and those found in food from yeasts, fungi, and bacteria that have been used in food preparation or contamination, as well as metabolites of sweeteners and antibiotics added to food are also reviewed.
Topics: Animals; Beverages; Biological Products; Fermentation; Food Analysis; Humans; Piperazines
PubMed: 25629623
DOI: 10.1080/10408398.2014.911142 -
Molecules (Basel, Switzerland) Jul 2023A series of novel Mannich bases were designed, synthesized, and screened for their antimicrobial activity. The target compounds were synthesized from...
A series of novel Mannich bases were designed, synthesized, and screened for their antimicrobial activity. The target compounds were synthesized from 4-(3-chlorophenyl)-5-(3-fluorophenyl)-2,4-dihydro-3-1,2,4-triazole-3-thione and different piperazine derivatives. The structures of the products were confirmed by H and C NMR and elemental analysis. The activity of piperazine derivatives against bacteria (Gram-positive: , , , , and ; Gram-negative: , , , and ) and yeasts (, , and ) was determined by the minimum inhibitory concentration and minimum bactericidal concentration values. Significant activity was observed against Gram-positive bacteria, mainly staphylococci (-) and bacteria of the genes of and (), as well as selected strains of Gram-negative bacteria, including bacteria of the family (), while all tested compounds showed high fungistatic activity against spp. yeasts, especially , with MICs ranging from 0.49 µg/mL () to 0.98 µg/mL () and 62.5 µg/mL (). In conclusion, the results obtained confirm the multidirectional antimicrobial activity of the newly synthesized piperazine derivatives. Furthermore, in silico studies suggest that the tested compounds are likely to have good oral bioavailability. The results obtained will provide valuable data for further research into this interesting group of compounds. The library of compounds obtained is still the subject of pharmacological research aimed at finding new interesting biologically active compounds.
Topics: Piperazine; Mannich Bases; Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Gram-Negative Bacteria; Candida; Anti-Infective Agents; Anti-Bacterial Agents
PubMed: 37513434
DOI: 10.3390/molecules28145562 -
Future Medicinal Chemistry Apr 2023The objective of the present study is to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores possessing antimicrobial/anticancer...
The objective of the present study is to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores possessing antimicrobial/anticancer activities. Twenty-four scaffolds were synthesized a click-inspired synthetic protocol and were assayed for anticancer activity using the methyl thiazolyl tetrazolium assay and for antimicrobial potency by serial dilution. Among all the tested 1,2,3-triazole scaffolds, compounds (IC: 5.22 ± 0.05 μM) and (IC: 5.34 ± 0.13 μM) exhibited good anticancer activity, and also showed notable antimicrobial activity. Molecular docking studies of potent analogs and were performed to provide an insight into their binding interactions. Compound is considered a valuable lead compound for further optimization of anticancer and antimicrobial agents.
Topics: Molecular Docking Simulation; Triazoles; Piperazine; Anti-Infective Agents; Structure-Activity Relationship; Antineoplastic Agents; Molecular Structure
PubMed: 37170810
DOI: 10.4155/fmc-2022-0316 -
Dalton Transactions (Cambridge, England... Jan 2021The piperazine scaffold is a privileged structure frequently found in biologically active compounds. Piperazine nucleus is found in many marketed drugs in the realm of... (Review)
Review
The piperazine scaffold is a privileged structure frequently found in biologically active compounds. Piperazine nucleus is found in many marketed drugs in the realm of antidepressants (amoxapine), antipsychotics (bifeprunox), antihistamines (cyclizine and oxatomide), antifungals (itraconazole), antibiotics (ciprofloxacin), etc. This is one of the reasons why piperazine based compounds are gaining prominence in today's research. In addition to the ring carbons, substitution in the nitrogen atom of piperazine not only creates potential drug molecules but also makes it unique with versatile binding possibilities with metal ions. Piperazine ring-based compounds find their application in biological systems with antihistamine, anticancer, antimicrobial and antioxidant properties. They have also been successfully used in the field of catalysis and metal organic frameworks (MOFs). The present review focuses on the synthesis and application of different piperazine derivatives and their metal complexes having diverse applications.
Topics: Chemistry Techniques, Synthetic; Coordination Complexes; Ligands; Piperazine
PubMed: 33416816
DOI: 10.1039/d0dt03569f -
International Urology and Nephrology Feb 2022Piperazine ferulate, a derivative of ferulic acid has been widely used in clinical practice for cardiovascular and kidney diseases in China. The objective of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Piperazine ferulate, a derivative of ferulic acid has been widely used in clinical practice for cardiovascular and kidney diseases in China. The objective of this meta-analysis was to investigate the benefits by adding piperazine ferulate to angiotensin receptor blockers (ARBs) in diabetic nephropathy patients.
METHODS
PubMed, Embase, Cochrane Library, Wangfang, VIP, and CNKI database (until March 17, 2021) were comprehensively searched for randomized controlled trials investigating the effects of adding piperazine ferulate to ARBs in diabetic nephropathy patients.
RESULTS
Data were retrieved from 14 RCTs involving 1374 patients. When compared with ARBs alone, co-administration of piperazine ferulate and ARBs significantly reduced urinary albumin excretion rate (weighted mean differences [WMD] - 20.32 μg/min; 95% confidence interval [CI] - 28.45 to - 12.19), 24-h proteinuria (WMD - 91.08 mg; 95% CI - 107.24 to - 74.91), β2-microglobulin (standard mean difference [SMD] - 2.07; 95% CI - 2.51 to - 1.63), serum level of creatinine (WMD - 8.39 μmol/L; 95% CI - 11.87 to - 4.92), fibrinogen (WMD - 0.40 g/L; 95% CI - 0.46 to - 0.33), and plasma viscosity (WMD - 0.56 mPa s; 95% CI - 0.91 to - 0.21). Subgroup analysis showed that the effects of piperazine ferulate on UAER and serum creatinine were stronger in early diabetic nephropathy. However, piperazine ferulate had no significant effects on the serum blood urea nitrogen and fasting blood glucose.
CONCLUSION
Adding piperazine ferulate to ARBs may achieve additional renal protective benefits, particular in early diabetic nephropathy patients.
Topics: Angiotensin Receptor Antagonists; Diabetic Nephropathies; Drug Therapy, Combination; Humans; Piperazine; Randomized Controlled Trials as Topic
PubMed: 34191230
DOI: 10.1007/s11255-021-02927-2 -
Journal of Medicinal Chemistry Jul 2023In search of new dual-acting histamine H/sigma-1 receptor ligands, we designed a series of compounds structurally based on highly active ligands previously studied and...
In search of new dual-acting histamine H/sigma-1 receptor ligands, we designed a series of compounds structurally based on highly active ligands previously studied and described by our team. However, we kept in mind that within the previous series, a pair of closely related compounds, and , differing only in the piperazine/piperidine moiety in the structural core showed a significantly different affinity at sigma-1 receptors (σRs). Therefore, we first focused on an in-depth analysis of the protonation states of piperazine and piperidine derivatives in the studied compounds. In a series of 16 new ligands, mainly based on the piperidine core, we selected three lead structures (, , and ) for further biological evaluation. Compound showed a broad spectrum of analgesic activity in both nociceptive and neuropathic pain models based on the novel molecular mechanism.
Topics: Humans; Histamine; Receptors, Histamine H3; Ligands; Nociception; Receptors, sigma; Piperazine; Piperidines; Neuralgia; Structure-Activity Relationship; Sigma-1 Receptor
PubMed: 37418295
DOI: 10.1021/acs.jmedchem.3c00430 -
Molecular Pharmaceutics Oct 2023Multidrug salts represent more than one drug in a crystal lattice and thus could be used to deliver multiple drugs in a single dose. It showcases unique physicochemical...
Multidrug salts represent more than one drug in a crystal lattice and thus could be used to deliver multiple drugs in a single dose. It showcases unique physicochemical properties in comparison to individual components, which could lead to improved efficacy and therapeutic synergism. This study presents the preparation and scale-up of sulfamethoxazole-piperazine salt, which has been thoroughly characterized by X-ray diffraction and thermal and spectroscopic analyses. A detailed mechanistic study investigates the impact of piperazine on the microenvironmental pH of the salt and its effect on the speciation profile, solubility, dissolution, and diffusion profile. Also, the improvement in the physicochemical properties of sulfamethoxazole due to the formation of salt was explored with lattice energy contributions. A greater ionization of sulfamethoxazole (due to pH changes contributed by piperazine) and lesser lattice energy of sulfamethoxazole-piperazine contributed to improved solubility, dissolution, and permeability. Moreover, the prepared salt addresses the stability issues of piperazine and exhibits good stability behavior under accelerated stability conditions. Due to the improvement of physicochemical properties, the sulfamethoxazole-piperazine salt demonstrates better pharmacokinetic parameters in comparison to sulfamethoxazole and provides a strong suggestion for the reduction of dose. The following study suggests that multidrug salts can concurrently enhance the physicochemical properties of drugs and present themselves as improved fixed-dose combinations.
Topics: Piperazine; Salts; X-Ray Diffraction; Solubility
PubMed: 37677085
DOI: 10.1021/acs.molpharmaceut.3c00646 -
Bioorganic Chemistry Jul 2021We synthesized eleven new amiridine-piperazine hybrids 5a-j and 7 as potential multifunctional agents for Alzheimer's disease (AD) treatment by reacting...
We synthesized eleven new amiridine-piperazine hybrids 5a-j and 7 as potential multifunctional agents for Alzheimer's disease (AD) treatment by reacting N-chloroacetylamiridine with piperazines. The compounds displayed mixed-type reversible inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Conjugates were moderate inhibitors of equine and human BChE with negligible fluctuation in anti-BChE activity, whereas anti-AChE activity was substantially dependent on N4-substitution of the piperazine ring. Compounds with para-substituted aromatic moieties (5g, 5h, and bis-amiridine 7) had the highest anti-AChE activity in the low micromolar range. Top-ranked compound 5h, N-(2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-9-yl)-2-[4-(4-nitro-phenyl)-piperazin-1-yl]-acetamide, had an IC for AChE = 1.83 ± 0.03 μM (K = 1.50 ± 0.12 and αK = 2.58 ± 0.23 μM). The conjugates possessed low activity against carboxylesterase, indicating a likely absence of unwanted drug-drug interactions in clinical use. In agreement with analysis of inhibition kinetics and molecular modeling studies, the lead compounds were found to bind effectively to the peripheral anionic site of AChE and displace propidium, indicating their potential to block AChE-induced β-amyloid aggregation. Similar propidium displacement activity was first shown for amiridine. Two compounds, 5c (R = cyclohexyl) and 5e (R = 2-MeO-Ph), exhibited appreciable antioxidant capability with Trolox equivalent antioxidant capacity values of 0.47 ± 0.03 and 0.39 ± 0.02, respectively. Molecular docking and molecular dynamics simulations provided insights into the structure-activity relationships for AChE and BChE inhibition, including the observation that inhibitory potencies and computed pK values of hybrids were generally lower than those of the parent molecules. Predicted ADMET and physicochemical properties of conjugates indicated good CNS bioavailability and safety parameters comparable to those of amiridine and therefore acceptable for potential lead compounds at the early stages of anti-AD drug development.
Topics: Acetylcholinesterase; Alzheimer Disease; Aminoquinolines; Animals; Antioxidants; Benzothiazoles; Butyrylcholinesterase; Cholinesterase Inhibitors; Dose-Response Relationship, Drug; Horses; Humans; Models, Molecular; Molecular Structure; Neuroprotective Agents; Oxidative Stress; Piperazine; Structure-Activity Relationship; Sulfonic Acids
PubMed: 34029971
DOI: 10.1016/j.bioorg.2021.104974